Masumoto lab | RIKEN BDR

Masumoto lab

Research Leader

Hidetoshi MasumotoM.D., Ph.D.

Photo of principal investigator

  • Location:Kobe / Developmental Biology Buildings
  • E-mail:hidetoshi.masumoto[at]riken.jpPlease replace [at] with @.

Realization of healthy longevity through development of iPS cell-based cardiovascular medicine

Research Summary

With an aging society such as Japan, the frequency of cardiovascular diseases (diseases affecting the heart and blood vessels) is expected to progressively increase in the future. Heart transplantation is an ultimate therapeutic modality for severe heart failure, however, the availability of hearts for transplantation is quite limited. Thus, there is a need to develop new therapies for severe heart failure to be able to treat more heart patients. Our laboratory is working on discoveries for new cardiovascular medicine through iPS cell technology-based cardiac regenerative therapy and drug discovery research, drawing on our lab head’s clinical experiences as a cardiovascular surgeon to design an experimental plan addressing clinical needs and to conduct studies using surgically established cardiovascular disease animal models. Our goal is to realize the healthy longevity of humans through the development of iPS cell-based cardiovascular medicine.

We are also actively working together with many research institutes and industry partners to advance clinical translational medicine. We are currently working to prepare clinical research studies for cardiac regenerative therapy using human iPS cells in collaboration with Kyoto University and industry partners.


Thick cardiac tissue sheets seen in culture dish

Three-dimensional thick cardiac tissue sheets generated from human iPS cells. Inset: Transplantation of the cardiac tissue sheet into a porcine myocardial infarction model (at MEDDEC, Port Island) (→: Cardiac tissue sheet)

Bio-engineered cardiac tissue capable of self-contraction and comprising various human iPS cell-derived heart cell types.

Histochemical staining of rat heart after transplantation

Transplantation of human iPS cell-derived cardiac tissue into a rat myocardial infarction model. Human myocardium with vascular network was formed in rat heart at 4 weeks after transplantation. Red: Human nucleic antigen, Green: von Willebrand factor (vascular endothelial cell) (Collaboration with University of Louisville, USA)

Research Theme

  • Cardiovascular regenerative medicine and drug discovery using iPS cell-derived 3-dimensional heart tissues
  • iPS cell-derived heart organoid research
  • Recapitulation of heart function using iPS cell-based organ-on-a-chip (heart-on-a-chip)
  • Translational research through collaboration with academia and industry

Main Publications List

  • Osada H, Kawatou M, Fujita D, et al.
    Therapeutic potential of clinical-grade human induced pluripotent stem cell-derived cardiac tissues.
    JTCVS Open (2021) doi: 10.1016/j.xjon.2021.09.038
  • Abulaiti M, Yalikun Y, Murata K, et al.
    Establishment of a heart-on-a-chip microdevice based on human iPS cells for the evaluation of human heart tissue function.
    Scientific Reports 10:19201 (2020) doi: 10.1038/s41598-020-76062-w
  • Ishigami M, Masumoto H, Ikuno T et al.
    Human iPS Cell-Derived Cardiac Tissue Sheets for Functional Restoration of Infarcted Porcine Hearts.
    PLoS One 13(8):e0201650 (2018) doi: 10.1371/journal.pone.0201650
  • Takeda M, Kanki Y, Masumoto H et al.
    Identification of Cardiomyocyte-Fated Progenitors From Human-Induced Pluripotent Stem Cells Marked With CD82.
    Cell Reports 22(2), 546-556 (2018) doi: 10.1016/j.celrep.2017.12.057
  • Kawatou M, Masumoto H, Fukushima H et al.
    Modelling Torsade De Pointes Arrhythmias in Vitro in 3D Human iPS Cell-Engineered Heart Tissue.
    Nature Communications 8(1):1078 (2017) doi: 10.1038/s41467-017-01125-y
  • Nakane T, Masumoto H, Tinney JP et al.
    Impact of Cell Composition and Geometry on Human Induced Pluripotent Stem Cells-Derived Engineered Cardiac Tissue.
    Scientific Reports 7:45641 (2017) doi: 10.1038/srep45641
  • Ikuno T, Masumoto H, Yamamizu K et al.
    Efficient and robust differentiation of endothelial cells from human induced pluripotent stem cells via lineage control with VEGF and cyclic AMP.
    PLoS One 12(4):e0176238 (2017) doi: 10.1371/journal.pone.0176238
  • Masumoto H, Nakane T, Tinney JP et al.
    The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages.
    Scientific Reports 6:29933 (2016) doi: 10.1038/srep29933
  • Matsuo T, Masumoto H, Tajima S et al.
    Efficient long-term survival of cell grafts after myocardial infarction with thick viable cardiac tissue entirely from pluripotent stem cells.
    Scientific Reports 5:16842 (2015) doi: 10.1038/srep16842
  • Masumoto H, Ikuno T, Takeda M et al.
    Human iPS cell-engineered cardiac tissue sheets with cardiomyocytes and vascular cells for cardiac regeneration.
    Scientific Reports 4:6716 (2014) doi: 10.1038/srep06716
  • Masumoto H, Matsuo T, Yamamizu K et al.
    Pluripotent stem cell-engineered cell sheets reassembled with defined cardiovascular populations ameliorate reduction in infarct heart function through cardiomyocyte-mediated neovascularization.
    Stem Cells 30(6), 1196-1205 (2012) doi: 10.1002/stem.1089

Member

Hidetoshi MasumotoResearch Leader /Senior Scientist hidetoshi.masumoto[at]riken.jp
Kozue MurataVisiting Scientist kozue.murata[at]riken.jp  
Yuko SasakiTechnical Staff I yuko.sasaki[at]riken.jp  
Maihemuti WusimanStudent Trainee wusiman.maihemuti[at]riken.jp  
Jun IidaStudent Trainee jun.iida[at]a.riken.jp  

*:concurrent / Please replace [at] with @.